JP2019108357A - 経口脱感作のための落花生処方物の製造 - Google Patents
経口脱感作のための落花生処方物の製造 Download PDFInfo
- Publication number
- JP2019108357A JP2019108357A JP2019034083A JP2019034083A JP2019108357A JP 2019108357 A JP2019108357 A JP 2019108357A JP 2019034083 A JP2019034083 A JP 2019034083A JP 2019034083 A JP2019034083 A JP 2019034083A JP 2019108357 A JP2019108357 A JP 2019108357A
- Authority
- JP
- Japan
- Prior art keywords
- peanut
- ara
- protein
- formulation
- lubricant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 235000020232 peanut Nutrition 0.000 title abstract description 152
- 235000010777 Arachis hypogaea Nutrition 0.000 title abstract description 143
- 235000017060 Arachis glabrata Nutrition 0.000 title abstract description 140
- 235000018262 Arachis monticola Nutrition 0.000 title abstract description 140
- 239000000203 mixture Substances 0.000 title abstract description 91
- 238000009472 formulation Methods 0.000 title abstract description 73
- 238000004519 manufacturing process Methods 0.000 title abstract description 21
- 241001553178 Arachis glabrata Species 0.000 title abstract 4
- 238000000586 desensitisation Methods 0.000 title description 4
- 238000000034 method Methods 0.000 abstract description 88
- 102000004169 proteins and genes Human genes 0.000 abstract description 84
- 108090000623 proteins and genes Proteins 0.000 abstract description 84
- 235000013312 flour Nutrition 0.000 abstract description 53
- 208000008267 Peanut Hypersensitivity Diseases 0.000 abstract description 14
- 238000009169 immunotherapy Methods 0.000 abstract description 6
- 238000011161 development Methods 0.000 abstract description 2
- 244000105624 Arachis hypogaea Species 0.000 description 153
- 239000000314 lubricant Substances 0.000 description 70
- 239000013566 allergen Substances 0.000 description 66
- 239000002775 capsule Substances 0.000 description 43
- 239000003085 diluting agent Substances 0.000 description 31
- 235000013305 food Nutrition 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 238000004007 reversed phase HPLC Methods 0.000 description 23
- 229920002472 Starch Polymers 0.000 description 21
- 229940032147 starch Drugs 0.000 description 21
- 239000008107 starch Substances 0.000 description 21
- 235000019698 starch Nutrition 0.000 description 21
- 239000000463 material Substances 0.000 description 20
- 239000000843 powder Substances 0.000 description 19
- 238000012360 testing method Methods 0.000 description 19
- 206010020751 Hypersensitivity Diseases 0.000 description 17
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- 238000003556 assay Methods 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- 239000000454 talc Substances 0.000 description 15
- 229910052623 talc Inorganic materials 0.000 description 15
- 235000012222 talc Nutrition 0.000 description 15
- 238000013329 compounding Methods 0.000 description 14
- 208000003455 anaphylaxis Diseases 0.000 description 13
- 239000000546 pharmaceutical excipient Substances 0.000 description 13
- 206010016946 Food allergy Diseases 0.000 description 12
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 12
- 239000008108 microcrystalline cellulose Substances 0.000 description 12
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 12
- 229940016286 microcrystalline cellulose Drugs 0.000 description 12
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 11
- 206010002198 Anaphylactic reaction Diseases 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 201000010853 peanut allergy Diseases 0.000 description 11
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 10
- 230000036783 anaphylactic response Effects 0.000 description 10
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 10
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 10
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 10
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 10
- 239000008101 lactose Substances 0.000 description 10
- 229960001375 lactose Drugs 0.000 description 10
- 229940068196 placebo Drugs 0.000 description 10
- 239000000902 placebo Substances 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 239000001506 calcium phosphate Substances 0.000 description 9
- 239000007963 capsule composition Substances 0.000 description 9
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 9
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 9
- 229940038472 dicalcium phosphate Drugs 0.000 description 9
- 239000000427 antigen Substances 0.000 description 8
- 108091007433 antigens Proteins 0.000 description 8
- 102000036639 antigens Human genes 0.000 description 8
- 238000005538 encapsulation Methods 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 230000000172 allergic effect Effects 0.000 description 7
- 230000002052 anaphylactic effect Effects 0.000 description 7
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000005070 sampling Methods 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 6
- 208000026935 allergic disease Diseases 0.000 description 6
- 208000030961 allergic reaction Diseases 0.000 description 6
- 208000010668 atopic eczema Diseases 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000002950 deficient Effects 0.000 description 6
- 210000003630 histaminocyte Anatomy 0.000 description 6
- 238000003119 immunoblot Methods 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 230000007815 allergy Effects 0.000 description 5
- 239000013590 bulk material Substances 0.000 description 5
- 239000013020 final formulation Substances 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 235000002639 sodium chloride Nutrition 0.000 description 5
- 208000004262 Food Hypersensitivity Diseases 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 235000010443 alginic acid Nutrition 0.000 description 4
- 229920000615 alginic acid Polymers 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 235000020932 food allergy Nutrition 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 235000003276 Apios tuberosa Nutrition 0.000 description 3
- 235000010744 Arachis villosulicarpa Nutrition 0.000 description 3
- 241000416162 Astragalus gummifer Species 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920001615 Tragacanth Polymers 0.000 description 3
- 239000000783 alginic acid Substances 0.000 description 3
- 229960001126 alginic acid Drugs 0.000 description 3
- 150000004781 alginic acids Chemical class 0.000 description 3
- -1 alkaline earth metal salts Chemical class 0.000 description 3
- 150000001413 amino acids Chemical group 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 210000003651 basophil Anatomy 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000013568 food allergen Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 229940079832 sodium starch glycolate Drugs 0.000 description 3
- 239000008109 sodium starch glycolate Substances 0.000 description 3
- 229920003109 sodium starch glycolate Polymers 0.000 description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 235000019750 Crude protein Nutrition 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 208000037656 Respiratory Sounds Diseases 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 206010047924 Wheezing Diseases 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000012550 audit Methods 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002485 combustion reaction Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229960000913 crospovidone Drugs 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000021474 generally recognized As safe (food) Nutrition 0.000 description 2
- 235000021473 generally recognized as safe (food ingredients) Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 231100001039 immunological change Toxicity 0.000 description 2
- 239000004816 latex Substances 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 235000021374 legumes Nutrition 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 235000014571 nuts Nutrition 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000005057 refrigeration Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 238000012384 transportation and delivery Methods 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- SFCPXHKCMRZQAC-UHFFFAOYSA-N 2,3-dihydroxypropyl benzoate Chemical compound OCC(O)COC(=O)C1=CC=CC=C1 SFCPXHKCMRZQAC-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical compound OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
- 240000002470 Amphicarpaea bracteata Species 0.000 description 1
- 235000000073 Amphicarpaea bracteata Nutrition 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 241000208223 Anacardiaceae Species 0.000 description 1
- 208000033399 Anaphylactic responses Diseases 0.000 description 1
- 208000028185 Angioedema Diseases 0.000 description 1
- 206010003402 Arthropod sting Diseases 0.000 description 1
- 241000238017 Astacoidea Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 244000056139 Brassica cretica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 1
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 235000009025 Carya illinoensis Nutrition 0.000 description 1
- 244000068645 Carya illinoensis Species 0.000 description 1
- 240000008886 Ceratonia siliqua Species 0.000 description 1
- 235000013912 Ceratonia siliqua Nutrition 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 241000723382 Corylus Species 0.000 description 1
- 235000007466 Corylus avellana Nutrition 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 244000303965 Cyamopsis psoralioides Species 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 241000698776 Duma Species 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 239000001692 EU approved anti-caking agent Substances 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 102000009438 IgE Receptors Human genes 0.000 description 1
- 108010073816 IgE Receptors Proteins 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 241000758791 Juglandaceae Species 0.000 description 1
- 238000007696 Kjeldahl method Methods 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 241000218652 Larix Species 0.000 description 1
- 235000005590 Larix decidua Nutrition 0.000 description 1
- 208000009481 Laryngeal Edema Diseases 0.000 description 1
- 206010023845 Laryngeal oedema Diseases 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101000980580 Mus musculus Mast cell protease 1 Proteins 0.000 description 1
- 241000237536 Mytilus edulis Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000002366 Nut Hypersensitivity Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000237502 Ostreidae Species 0.000 description 1
- 239000008118 PEG 6000 Substances 0.000 description 1
- 240000001090 Papaver somniferum Species 0.000 description 1
- 235000008753 Papaver somniferum Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241000237503 Pectinidae Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 240000006711 Pistacia vera Species 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 235000003434 Sesamum indicum Nutrition 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 240000001058 Sterculia urens Species 0.000 description 1
- 235000015125 Sterculia urens Nutrition 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000006578 abscission Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 230000002009 allergenic effect Effects 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 229940009868 aluminum magnesium silicate Drugs 0.000 description 1
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 235000020113 brazil nut Nutrition 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 235000009120 camo Nutrition 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 235000020226 cashew nut Nutrition 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000005513 chalcones Nutrition 0.000 description 1
- 235000005607 chanvre indien Nutrition 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 238000009841 combustion method Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 239000005712 elicitor Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 239000013569 fungal allergen Substances 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 231100001014 gastrointestinal tract lesion Toxicity 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 239000011487 hemp Substances 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000017307 interleukin-4 production Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 239000000832 lactitol Substances 0.000 description 1
- 235000010448 lactitol Nutrition 0.000 description 1
- 229960003451 lactitol Drugs 0.000 description 1
- VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
- 229960001021 lactose monohydrate Drugs 0.000 description 1
- 235000005772 leucine Nutrition 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 241000238565 lobster Species 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229940037627 magnesium lauryl sulfate Drugs 0.000 description 1
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 235000020638 mussel Nutrition 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229940124624 oral corticosteroid Drugs 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000020636 oyster Nutrition 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 235000021400 peanut butter Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 235000020233 pistachio Nutrition 0.000 description 1
- 239000013573 pollen allergen Substances 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 235000020637 scallop Nutrition 0.000 description 1
- 235000014102 seafood Nutrition 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000000357 thermal conductivity detection Methods 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000020234 walnut Nutrition 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4833—Encapsulating processes; Filling of capsules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/35—Allergens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4875—Compounds of unknown constitution, e.g. material from plants or animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/542—Mucosal route oral/gastrointestinal
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Botany (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Pulmonology (AREA)
- Transplantation (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
Description
本出願は、米国特許仮出願第61/784,964号(2013年3月14日出願)(この記載内容は参照により本明細書中に組み入れられる)の利益を主張する。
本明細書中で言及される出版物、特許および特許出願はすべて、各々独立の出版物、特許または特許出願が参照により組み入れられることを具体的に且つ独立して示された場合と同程度に参照により本明細書中に組み入れられる。
本明細書中で開示されるのは、落花生アレルギーの処置のための薬学的組成物を製造するために用いられ得るラッカセイ粉からタンパク質を単離するシステムおよび方法である。当該システムおよび方法は、高圧(相)液体クロマトグラフィー(HPLC)を利用して、落花生粉からAra h1、Ara h2およびAra h6を捕捉する。
別記しない限り、本明細書中で用いられる技術用語および科学用語はすべて、本明細書中に記載される本発明が属する当該技術分野の当業者に一般に理解されるものと同じ意味を有する。本明細書中で言及される特許および出版物はすべて、参照により本明細書中に組み入れられる。
本明細書中に記載される処方物は、1つ以上の活性成分を含む。活性成分は、任意の供給元、例えばGolden Peanut Companyから入手され得るラッカセイ粉から単離され得る。落花生粉は、軽く炒った落花生から粉砕される約10%から約15%まで、または約12%脱脂落花生粉であり得る。落花生粉は、いくつかの場合、内容物および生物学の標準分析後、供給者により放出され、冷蔵下で9〜12ヶ月間安定であり得る。落花生粉は、被験者への投与の前に、処方され、カプセル封入され、そして試験され得る。
RP−HPLCピークプロフィールが、Ara h1、Ara h2およびAra h6を実際に分離し、同定することを確証するために、各ピークから単離される材料は、例えば4〜20Novexトリス−HClプレキャストゲルを用いて、SDSポリアクリルアミドゲル電気泳動により特性化され得る(例えば、図5参照)。付加的ゲルが二フッ化ポリビニリデン(PVDF)膜に移動され、イムノブロッティングのために加工処理されて、Ara h1、Ara h2およびAra h6ニワトリ抗血清と反応させられて、例えばJong et al.(EMBO J.,1988;7(3):745−750)により記載された検定方法を用いて、ホースラディッシュペルオキシダーゼ共役ヤギ抗ニワトリIgGで展開され得る。抽出物は焙煎落花生粉に由来し得るが、抗血清は、生落花生抽出物から精製されるAra hタンパク質に対して生成され得る、ということに留意すべきである。抗血清は、生落花生に、そして焙煎落花生抽出物から得られる単離Ara hタンパク質に由来する対照Ara hタンパク質の両方と反応する(例えば、図6参照)。
本明細書中に記載される処方物中に用いるための落花生粉(PF)は、任意の信頼できる生産者、例えば落花生粉および落花生油(焙煎落花生の脱脂の副産物)を製造するGolden Peanut Company(GPC)(これに限定されない)から供給され得る。
PF原材料は、cGMP生成のための放出前に、外見、同一性、総タンパク質含量および含水量に関して試験され得る(例えば、表4参照)。PFは、2〜8℃で制御条件下で保存され得る。
表5は、本明細書中に記載される処方物中に用いられ得る賦形剤例を提供する。本明細書中に記載される処方物中に用いられ得るその他の賦形剤は、説明の別の箇所で提供される。
落花生粉(落花生アレルゲンタンパク質Ara h1、Ara h2およびAra h6を含有)は、漸増用量で嵩高剤および流動化剤とともに処方され、0.5mg、1mg、10mg、100mgおよび1000mgの各々の落花生タンパク質を含有するカプセルからなる。
図7および表6は、0.5mgの落花生タンパク質および1mgの落花生タンパク質カプセルを含む低用量カプセルに関して提唱された配合工程を要約する。
図8および表7は、10mgの落花生タンパク質、100mgの落花生タンパク質および475mgの落花生タンパク質カプセルを含む高用量カプセルに関する提唱配合工程を要約する。
配合の24時間以内に、処方物はカプセル中に充填され得る。
化学および製造組成物の概観
落花生粉(落花生アレルゲンタンパク質Ara h1、Ara h2およびAra h6を含有)は、漸増用量で嵩高剤および流動化剤とともに処方され、約0.5mg、約1mg、約10mg、約100mg、約475mgまたは約1000mgの各々の落花生タンパク質を、1つ以上の希釈剤、1つ以上の滑剤、1つ以上の潤滑剤とともに含むカプセルを包含する。任意に、1つ以上の充填剤が付加され得る。各カプセルは、開けられて、投与直前に味遮蔽食物中に内容物が混合され得る。
カプセル封入方法/設備は、開発バッチにおける充填重量変動査定に基づいて決定され得る。製造過程の制御は、定期的重量検査を含み得る。
バルク物質(例えば、1つ以上の調製ステップ中の、および/またはカプセル封入間前の最終混合物の処方物)および処方物に関して、外見査定を実施し得る。外見の査定としては、例えば完全スペクトル光により照明される白色バックグラウンドに対して容器を視覚的に検査することからなる。
カプセルの内容物均一性(CU)は、USP標準に従った実施され得る。内容物均一性は、総タンパク質窒素内容物燃焼検定を基礎にし得る。意図は、すべての用量で個々のカプセルを検定することを可能にする感受性で燃焼機器を同定することである。
カプセルを計量し、内容物を空にして、空のカプセルを計量することにより、カプセル送達可能質量が評価され得る。次いで、送達量%が算定され得る。
含水量は、タンパク質の安定性に影響を及ぼし得るので、経時的含水量の変化を理解することは、いくつかの場合、保存寿命を短くすることもある処方物中の変化を理解するために有用である。落花生粉充填カプセルに関して、含水量は、USPに従って乾燥減量(LOD)決定試験を用いて測定され得る。LODのための条件は、賦形剤要件、ならびに落花生粉に関する要件に基づいて確定され得る。
RP−HPLCを用いて、PF、BSおよび最終処方物の同一性を確証し得る。(Attorney Docket No.43567−702.101)と同一日に出願された表題「落花生処方物およびその使用(Peanut Formulations and Uses Thereof)」の関連出願(この記載内容は参照により本明細書中に組み入れられる)にさらに詳細に記載された方法に従って、試料は分析され得るし、その結果生じるクロマトグラムは、試験方法で提供されるクロマトグラム例と比較され得る(例えば、図9参照)。
落花生粉中の総抽出可能タンパク質の確定と類似のアプローチが、カプセル処方物中の総抽出可能タンパク質の確定のために用いられ得る。当該アプローチは、全強度に関して評価され得る。要するに、カプセル内容物は、空にされ、計量され、RP−HPLCにより分析され得る。この手法を用いる落花生粉試料のクロマトグラフィー分析は、落花生粉抽出物に独特であるクロマトグラフィー的「指紋」を生じる。約12分〜35分の間に溶離する試料の領域は、統合され得る。統合される総面積は、BSA基準に対して定量され得る。次いで、総抽出可能タンパク質含量が、以下の方程式を用いて算定され得る。
Rs=すべての作業基準における平均BSAピーク面積。
CSTD=BSA作業基準濃度(mg/mL);
VSample=作業試料の総希釈剤容積(10.0 mL);および
Wtsample=落花生粉試料の重量(g))。
RP−HPLC法を用いて抽出される試料のクロマトグラフィー分析は、落花生粉抽出物に独特のクロマトグラフィー「指紋」、ならびにAra h1、Ara h2およびAra h6に対応する領域の相対比を生じ得る(例えば、図1参照)。これらの領域の各々のタンパク質含量(mg/g)は、上記の方程式によって定量され得る。次に、以下の方程式に従って、各領域に関する総タンパク質の相対含量パーセントが算定される。
充填済みカプセル中のタンパク質含量は、落花生粉の場合と同様に確定され得る(AOCS Official Method Ba 4e−93)。精確なタンパク質含量決定は、試料の窒素含量によって決まり得るため、窒素を含有する賦形剤は処方物中に用いられ得ない。当該方法はデュマ法に基づいており、そして純酸素中の粗タンパク質の燃焼、ならびに放出される窒素ガスの測定に基づいている。用いられ得る方法は、AOCS Official Method Ba 4e−93であり得る。AOCS法の定義および範囲は、以下で提供される。
処方物は、2〜8℃で保存され得る。加速されたそして長期の安定性を査定するために、処方物は、表11および表12に記載される頻度および明細によって試験され得る。外見/色、水分、同一性および強度に関する試験は、すべての時点で実施され得るし、汚染微生物数は、年1回、12、24および36か月目に実施され得る。
本明細書中に記載される方法を用いて調製される薬学的組成物は、生成物の粘稠性に関して落花生タンパク質の種々のロットを比較するために用いられ得る。
(1)
特性化落花生タンパク質を含む落花生粉の低用量カプセル処方物の製造方法であって、以下の:
(a)第一配合で落花生粉および希釈剤を混合することと、
(b)第二配合で約45%の希釈剤を付加することと、
(c)第三配合で残りの希釈剤を付加することと、
(d)最終配合で滑剤および/または潤滑剤を付加することと、
(e)カプセル中に配合粉末を封入することと
を包含する方法。
(2)
ステップ(a)の希釈剤がデンプンを含む、(1)に記載の方法。
(3)
ステップ(b)および/または(c)の希釈剤が、デンプン、ラクトース、微晶質セルロース(アビセル(登録商標))またはリン酸二カルシウムを含む、(1)に記載の方法。
(4)
ステップ(d)の滑剤が、コロイド二酸化ケイ素(Cab−O−Sil)、タルク(例えば、ウルトラタルク4000)およびその組合せからなる群から選択される、(1)に記載の方法。
(5)
前記滑剤がCab−O−Silを含む、(1)に記載の方法。
(6)
ステップ(d)の潤滑剤がステアリン酸マグネシウムを含む、(1)に記載の方法。
(7)
ステップ(d)が、滑剤または潤滑剤を付加することを包含する、(1)に記載の方法。
(8)
ステップ(d)が、滑剤および潤滑剤を付加することを包含する、(1)に記載の方法。
(9)
カプセル封入前に配合混合物をサンプリングすることをさらに包含する、(1)に記載の方法。
(10)
前記用量が、約0.5または約1.0mgの落花生タンパク質を含む、(1)に記載の方法。
(11)
ステップ(d)が、前記配合材料をメッシュスクリーンに通すことをさらに包含する、(1)に記載の方法。
(12)
本明細書中に提供されるカプセル処方物の製造方法であって、
(a)第一配合で落花生粉および希釈剤を混合することと、
(b)配合材料を放出することと、
(c)前記配合材料をメッシュスクリーンに通して、第二配合でスクリーン済み材料を配合することと、
(d)最終配合で滑剤および/または潤滑剤を付加することと、
(e)配合粉末をカプセル封入することとを包含する方法。
(13)
カプセル封入前に1回以上、ステップ(d)の配合材料を任意にサンプリングすることをさらに包含する、(12)に記載の方法。
(14)
前記用量が、約10、約100または約475mgの落花生タンパク質を含む、(12)に記載の方法。
(15)
ステップ(a)の希釈剤が、デンプン、ラクトース、微晶質セルロース(アビセル(登録商標))またはリン酸二カルシウムを含む、(12)に記載の方法。
(16)
ステップ(c)のメッシュスクリーンが#20メッシュスクリーンを含む、(12)に記載の方法。
(17)
ステップ(d)の滑剤が、コロイド二酸化ケイ素(Cab−O−Sil)、タルク(例えば、ウルトラタルク4000)およびその組合せからなる群から選択される、(12)に記載の方法。
(18)
前記滑剤がCab−O−Silを含む、(12)に記載の方法。
(19)
ステップ(d)の潤滑剤がステアリン酸マグネシウムを含む、(12)に記載の方法。
(20)
ステップ(d)が滑剤または潤滑剤を付加することを包含する、(12)に記載の方法。
(21)
ステップ(d)が滑剤および潤滑剤を付加すること包含する(12)に記載の方法。
(22)
本明細書中で提供される、本明細書で提供される方法に有用なカプセル処方物の製造方法であって、
(a)落花生粉、希釈剤、滑剤および/または潤滑剤を混合することと、
(b)配合材料を放出することと、
(c)前記配合材料をメッシュスクリーンに通すことと、
(d)配合粉末をカプセル封入することと
を包含する方法。
(23)
前記用量が約10または約100mgの落花生タンパク質を含む、(22)に記載の方法。
(24)
前記落花生粉が特性化落花生タンパク質を含む(1)〜(23)のいずれかに記載の方法。
(25)
前記落花生タンパク質がAra h1、Ara h2およびAra h6を含む、(24)に記載の方法。
(26)
Ara h1、Ara h2およびAra h6の濃度がRP−HPLCにより特性化される、(25)に記載の方法。
(27)
Ara h1、Ara h2およびAra h6の濃度が少なくとも参照標準の量である、(26)に記載の方法。
(28)
カプセル封入処方物が、少なくとも約3、6、9、12、18、24、36か月またはそれ以上の間安定である、(1)〜(27)のいずれかに記載の方法。
(29)
前記カプセル封入処方物が、約2℃から約8℃まで、または約20℃から約30℃までの温度で安定である、(1)〜(28)のいずれかに記載の方法。
(30)
前記カプセル封入処方物が約25℃の温度で安定である、(29)に記載の方法。
(31)
前記カプセルのサイズが3,00または000である、(1)〜(30)のいずれかに記載の方法。
(32)
前記カプセルがヒドロキシプロピルメチルセルロース(HPMC)を含む、(1)〜(31)のいずれかに記載の方法。
(33)
容器手段中に前記処方物を保存することをさらに包含する、(1)〜(32)のいずれかに記載の方法。
(34)
前記容器手段がボトルである、(33)に記載の方法。
(35)
前記ボトルが黄褐色ボトルである、(34)に記載の方法。
(36)
前記容器手段が、前記容器手段の含水量を制御するために防湿剤ポケットをさらに含む、(33)に記載の方法。
Claims (1)
- 明細書に記載の発明。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2021025462A JP7454519B2 (ja) | 2013-03-14 | 2021-02-19 | 経口脱感作のための落花生処方物の製造 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361784964P | 2013-03-14 | 2013-03-14 | |
US61/784,964 | 2013-03-14 | ||
JP2016501522A JP6752140B2 (ja) | 2013-03-14 | 2014-03-12 | 経口脱感作のための落花生処方物の製造 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016501522A Division JP6752140B2 (ja) | 2013-03-14 | 2014-03-12 | 経口脱感作のための落花生処方物の製造 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021025462A Division JP7454519B2 (ja) | 2013-03-14 | 2021-02-19 | 経口脱感作のための落花生処方物の製造 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2019108357A true JP2019108357A (ja) | 2019-07-04 |
JP6891205B2 JP6891205B2 (ja) | 2021-06-18 |
Family
ID=51528061
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016501522A Active JP6752140B2 (ja) | 2013-03-14 | 2014-03-12 | 経口脱感作のための落花生処方物の製造 |
JP2019034083A Active JP6891205B2 (ja) | 2013-03-14 | 2019-02-27 | 経口脱感作のための落花生処方物の製造 |
JP2021025462A Active JP7454519B2 (ja) | 2013-03-14 | 2021-02-19 | 経口脱感作のための落花生処方物の製造 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016501522A Active JP6752140B2 (ja) | 2013-03-14 | 2014-03-12 | 経口脱感作のための落花生処方物の製造 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021025462A Active JP7454519B2 (ja) | 2013-03-14 | 2021-02-19 | 経口脱感作のための落花生処方物の製造 |
Country Status (18)
Country | Link |
---|---|
US (5) | US9198869B2 (ja) |
EP (3) | EP2968529B1 (ja) |
JP (3) | JP6752140B2 (ja) |
CN (2) | CN109125283A (ja) |
AU (5) | AU2014240404B2 (ja) |
BR (1) | BR112015021756B1 (ja) |
CA (1) | CA2903229A1 (ja) |
DK (2) | DK3482771T3 (ja) |
ES (2) | ES2940686T3 (ja) |
FI (2) | FI3482771T3 (ja) |
FR (1) | FR23C1026I1 (ja) |
HK (1) | HK1217660A1 (ja) |
HU (1) | HUE051831T2 (ja) |
MX (1) | MX2015010315A (ja) |
PL (1) | PL2968529T3 (ja) |
PT (1) | PT2968529T (ja) |
SI (1) | SI2968529T1 (ja) |
WO (1) | WO2014159607A1 (ja) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2924349B1 (fr) | 2007-12-03 | 2010-01-01 | Dbv Tech | Methode de desensibilitation aux allergenes |
DK3482771T3 (da) * | 2013-03-14 | 2023-03-20 | Nestle Sa | Fremstilling af jordnøddeformuleringer til oral desensibilisering |
US9492535B2 (en) | 2013-03-14 | 2016-11-15 | Aimmune Therapeutics, Inc. | Peanut formulations and uses thereof |
WO2016033094A1 (en) | 2014-08-25 | 2016-03-03 | Aimmune Therapeutics, Inc. | Egg protein formulations and methods of manufacture thereof |
MA41020A (fr) | 2014-11-25 | 2017-10-03 | Evelo Biosciences Inc | Compositions probiotiques et prébiotiques, et leurs procédés d'utilisation pour la modulation du microbiome |
US10064936B2 (en) | 2015-02-20 | 2018-09-04 | The Board Of Trustees Of The Leland Stanford Junior University | Mixed allergen compositions and methods for using the same |
US10166286B2 (en) | 2015-02-20 | 2019-01-01 | The Board Of Trustees Of The Leland Stanford Junior University | Mixed allergen compositions and methods for using the same |
US10143742B2 (en) | 2015-02-20 | 2018-12-04 | The Board Of Trustees Of The Leland Stanford Junior University | Mixed allergen compositions and methods for using the same |
US11452774B2 (en) | 2015-02-20 | 2022-09-27 | The Board Of Trustees Of The Leland Stanford Junior University | Mixed allergen compositions and methods for using the same |
US10149904B2 (en) | 2015-02-20 | 2018-12-11 | The Board Of Trusteees Of The Leland Stanford Junior University | Mixed allergen compositions and methods for using the same |
TW201709926A (zh) * | 2015-04-23 | 2017-03-16 | 賽諾菲公司 | 用於舌下投藥之吡喃葡萄糖基脂a及過敏原調配物 |
US10856567B2 (en) | 2016-07-22 | 2020-12-08 | Kari Brown | Baby food products containing allergenic proteins and methods of delivering same |
ES2950506T3 (es) * | 2016-12-05 | 2023-10-10 | Reacta Biotech Ltd | Formulaciones de alimentos para pruebas alimentarias orales |
CA3050093A1 (en) * | 2017-01-13 | 2018-07-19 | Aimmune Therapeutics, Inc. | Methods of manufacture of nut flours and formulations for oral immunotherapy |
BR102017026619A2 (pt) | 2017-02-15 | 2018-10-30 | Euroimmun Medizinische Labordiagnostika Ag | ensaio melhorado para a diagnose de alergia a amendoim |
CN111465328A (zh) | 2017-07-18 | 2020-07-28 | 前品牌股份有限公司 | 制备混合型变应原组合物的方法 |
US11369676B2 (en) | 2017-11-02 | 2022-06-28 | Société des Produits Nestlé S.A. | Methods of oral immunotherapy |
GB201718342D0 (en) * | 2017-11-06 | 2017-12-20 | Cambridge Allergy Ltd | Allergenic protein formulations for immunotherapy |
CA3107667A1 (en) | 2018-07-27 | 2020-01-30 | Aimmune Therapeutics, Inc. | Oral immunotherapy unit dose dispensing systems and methods |
CA3122854A1 (en) * | 2018-12-17 | 2020-06-25 | Aimmune Therapeutics, Inc. | Formulations for egg oral immunotherapy, methods of manufacture, and treatments for egg allergy |
CN113891722A (zh) * | 2018-12-20 | 2022-01-04 | 爱沐疗法公司 | 用于漏服剂量的花生口服免疫疗法给药计划表 |
US11766477B2 (en) | 2019-01-23 | 2023-09-26 | Societe Des Produits Nestle S.A. | Methods for making mixed allergen compositions |
CA3137295A1 (en) | 2019-05-10 | 2020-11-19 | Aimmune Therapeutics, Inc. | Methods for improving the quality of life of a patient with a peanut allergy |
EP4009959A1 (en) * | 2019-08-08 | 2022-06-15 | Evonik Operations GmbH | Method of preparing a solid dosage form and a lubricant |
EP4081251A4 (en) * | 2019-12-23 | 2024-03-20 | Prota Therapeutics Pty Ltd | PHARMACEUTICAL COMPOSITIONS |
CA3204515A1 (en) | 2021-01-08 | 2022-07-14 | Jamie M. Orengo | Methods for treating peanut allergy and enhancing peanut allergen-specific immunotherapy by administering an il-4r antagonist |
WO2023198674A1 (en) | 2022-04-11 | 2023-10-19 | Alk-Abelló A/S | Peanut allergen composition |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003128697A (ja) * | 1994-09-10 | 2003-05-08 | Hayashibara Biochem Lab Inc | ペプチドとその用途 |
JP2006519187A (ja) * | 2003-02-28 | 2006-08-24 | アルカベロ アクチェセルスカプ | 糖類マトリックスを有する剤形 |
JP2009522258A (ja) * | 2005-12-28 | 2009-06-11 | テバ ファーマシューティカル インダストリーズ リミティド | 増大したバイオアベイラビリティを有するフェノフィブラートの医薬製剤 |
WO2011098499A1 (en) * | 2010-02-12 | 2011-08-18 | Centro De Ingeniería Genética Y Biotecnología (Cigb) | Orally administrable pharmaceutical pellet of epidermal growth factor |
JP2011225525A (ja) * | 2010-03-30 | 2011-11-10 | Nitto Denko Corp | 安定化医薬組成物、安定化医薬組成物溶液製剤、フィルム状製剤及びフィルム状製剤の製造方法 |
WO2012123759A1 (en) * | 2011-03-17 | 2012-09-20 | Cambridge Enterprise Limited | Treatment for peanut allergy |
JP2013505897A (ja) * | 2009-07-28 | 2013-02-21 | メチレーション・サイエンシーズ・インターナショナル・ソサイアティーズ・ウィズ・リストリクティッド・ライアビリティ | S−アデノシルメチオニン製剤の改善された薬物動態 |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3809767A (en) * | 1969-05-12 | 1974-05-07 | Griffith Laboratories | Methods of making vegetable protein concentrates |
WO1992015285A1 (en) | 1991-03-01 | 1992-09-17 | Warner-Lambert Company | Starch-based controlled release compositions |
US20120164306A1 (en) * | 1993-08-03 | 2012-06-28 | Girsh Leonard S | Process for preparing hypoallergenic and reduced fat foods |
AU2065801A (en) | 1999-12-06 | 2001-06-12 | Panacea Pharmaceuticals, Llc | Passive desensitization |
DK1272213T3 (da) | 2000-04-06 | 2006-07-10 | Seer Pharmaceuticals Llc | Mikrobielt afgivelsessystem |
US7820175B2 (en) * | 2004-03-19 | 2010-10-26 | Herbal Spring, Llc | Herbal therapy for the treatment of food allergy |
FR2924349B1 (fr) * | 2007-12-03 | 2010-01-01 | Dbv Tech | Methode de desensibilitation aux allergenes |
MX2011005168A (es) | 2008-11-19 | 2011-05-30 | Avantor Performance Mat Inc | Excipiente basado en celulosa microcristalina granular, directamente compresible, procesos de fabricacion y uso del mismo. |
US8399519B2 (en) | 2008-12-19 | 2013-03-19 | Merz Pharma Gmbh & Co. Kgaa | 1-amino-alkylcyclohexane derivatives for the treatment of mast cell mediated diseases |
UY33472A (es) * | 2010-06-30 | 2012-01-31 | Novartis Ag | ?composiciones farmacéuticas que comprenden monohidrato de lactato de 4-amino-5-fluoro-3-[6-(4-metil-piperazin-1-il)-1hbencimidazol-2-il]-1h-quinolin-2-ona?. |
CN101912364B (zh) * | 2010-08-09 | 2015-07-15 | 刘会梅 | 银杏内酯b脂质体组合药物 |
ES2936312T3 (es) * | 2011-08-31 | 2023-03-16 | Perosphere Tech Inc | Métodos para la desensibilización eficaz y rápida de pacientes alérgicos |
WO2013087119A1 (en) * | 2011-12-16 | 2013-06-20 | Hal Allergy Holding B.V. | Pharmaceutical formulations and the use thereof for the treatment of peanut allergy |
DK3482771T3 (da) | 2013-03-14 | 2023-03-20 | Nestle Sa | Fremstilling af jordnøddeformuleringer til oral desensibilisering |
US9492535B2 (en) * | 2013-03-14 | 2016-11-15 | Aimmune Therapeutics, Inc. | Peanut formulations and uses thereof |
WO2016033094A1 (en) | 2014-08-25 | 2016-03-03 | Aimmune Therapeutics, Inc. | Egg protein formulations and methods of manufacture thereof |
CA3050093A1 (en) | 2017-01-13 | 2018-07-19 | Aimmune Therapeutics, Inc. | Methods of manufacture of nut flours and formulations for oral immunotherapy |
US11369676B2 (en) | 2017-11-02 | 2022-06-28 | Société des Produits Nestlé S.A. | Methods of oral immunotherapy |
-
2014
- 2014-03-12 DK DK18213124.3T patent/DK3482771T3/da active
- 2014-03-12 DK DK14776121.7T patent/DK2968529T3/da active
- 2014-03-12 US US14/207,165 patent/US9198869B2/en active Active
- 2014-03-12 CN CN201811093370.9A patent/CN109125283A/zh active Pending
- 2014-03-12 SI SI201431687T patent/SI2968529T1/sl unknown
- 2014-03-12 JP JP2016501522A patent/JP6752140B2/ja active Active
- 2014-03-12 BR BR112015021756-7A patent/BR112015021756B1/pt active IP Right Grant
- 2014-03-12 EP EP14776121.7A patent/EP2968529B1/en active Active
- 2014-03-12 EP EP18213124.3A patent/EP3482771B1/en active Active
- 2014-03-12 PL PL14776121T patent/PL2968529T3/pl unknown
- 2014-03-12 HU HUE14776121A patent/HUE051831T2/hu unknown
- 2014-03-12 ES ES18213124T patent/ES2940686T3/es active Active
- 2014-03-12 PT PT147761217T patent/PT2968529T/pt unknown
- 2014-03-12 ES ES14776121T patent/ES2826224T3/es active Active
- 2014-03-12 AU AU2014240404A patent/AU2014240404B2/en active Active
- 2014-03-12 MX MX2015010315A patent/MX2015010315A/es unknown
- 2014-03-12 CA CA2903229A patent/CA2903229A1/en active Pending
- 2014-03-12 FI FIEP18213124.3T patent/FI3482771T3/fi active
- 2014-03-12 WO PCT/US2014/024401 patent/WO2014159607A1/en active Application Filing
- 2014-03-12 CN CN201480013792.4A patent/CN105101994B/zh active Active
- 2014-03-12 EP EP21199373.8A patent/EP3998080A1/en active Pending
-
2015
- 2015-10-13 US US14/881,437 patent/US20160030289A1/en not_active Abandoned
-
2016
- 2016-05-20 HK HK16105808.3A patent/HK1217660A1/zh unknown
- 2016-09-21 AU AU2016231523A patent/AU2016231523B2/en active Active
-
2017
- 2017-10-24 US US15/792,716 patent/US10449118B2/en active Active
-
2018
- 2018-08-30 AU AU2018222980A patent/AU2018222980A1/en not_active Abandoned
-
2019
- 2019-02-27 JP JP2019034083A patent/JP6891205B2/ja active Active
- 2019-06-26 US US16/453,871 patent/US11141352B2/en active Active
-
2020
- 2020-04-22 AU AU2020202685A patent/AU2020202685B2/en active Active
-
2021
- 2021-02-19 JP JP2021025462A patent/JP7454519B2/ja active Active
-
2022
- 2022-03-17 AU AU2022201858A patent/AU2022201858B2/en active Active
- 2022-09-20 US US17/948,611 patent/US20230120350A1/en active Pending
-
2023
- 2023-07-04 FI FIC20230022C patent/FIC20230022I1/fi unknown
- 2023-07-07 FR FR23C1026C patent/FR23C1026I1/fr active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003128697A (ja) * | 1994-09-10 | 2003-05-08 | Hayashibara Biochem Lab Inc | ペプチドとその用途 |
JP2006519187A (ja) * | 2003-02-28 | 2006-08-24 | アルカベロ アクチェセルスカプ | 糖類マトリックスを有する剤形 |
JP2009522258A (ja) * | 2005-12-28 | 2009-06-11 | テバ ファーマシューティカル インダストリーズ リミティド | 増大したバイオアベイラビリティを有するフェノフィブラートの医薬製剤 |
JP2013505897A (ja) * | 2009-07-28 | 2013-02-21 | メチレーション・サイエンシーズ・インターナショナル・ソサイアティーズ・ウィズ・リストリクティッド・ライアビリティ | S−アデノシルメチオニン製剤の改善された薬物動態 |
WO2011098499A1 (en) * | 2010-02-12 | 2011-08-18 | Centro De Ingeniería Genética Y Biotecnología (Cigb) | Orally administrable pharmaceutical pellet of epidermal growth factor |
JP2011225525A (ja) * | 2010-03-30 | 2011-11-10 | Nitto Denko Corp | 安定化医薬組成物、安定化医薬組成物溶液製剤、フィルム状製剤及びフィルム状製剤の製造方法 |
WO2012123759A1 (en) * | 2011-03-17 | 2012-09-20 | Cambridge Enterprise Limited | Treatment for peanut allergy |
Non-Patent Citations (3)
Title |
---|
ALLERGY, vol. Vol.67, Suppl.96, JPN6018041535, 2012, pages 548 - 1463, ISSN: 0004211025 * |
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 55, JPN6018041536, 2007, pages 4461 - 4473, ISSN: 0004211026 * |
SINGH H. ET AL.: "Developing RP-HPLC method for detection of peanut allergens", AACC INTERNATIONAL ANNUAL MEETING, JPN6018041537, 2011, ISSN: 0004211027 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7454519B2 (ja) | 経口脱感作のための落花生処方物の製造 | |
JP7012929B2 (ja) | タマゴのタンパク質製剤およびその製造方法 | |
JP2022136170A (ja) | 経口免疫療法用のナッツ粉および製剤の製造方法 | |
WO2014159609A1 (en) | Peanut formulations and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20190319 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190328 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20190320 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190416 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200210 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200430 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200721 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20201021 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210219 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20210219 |
|
C11 | Written invitation by the commissioner to file amendments |
Free format text: JAPANESE INTERMEDIATE CODE: C11 Effective date: 20210303 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20210402 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20210405 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20210511 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210526 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6891205 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: R3D02 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |